Genetic Variant DACH1:p.Gly81dup (chr13-71866526-T-TGCC) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_080759.6(DACH1):c.241_243dupGGC(p.Gly81dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,229,430 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 6)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

DACH1
NM_080759.6 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

2 publications found

Variant links:

Genes affected

DACH1 (HGNC:2663): (dachshund family transcription factor 1) This gene encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression and cell fate determination during development. The protein contains a Ski domain that is highly conserved from Drosophila to human. Expression of this gene is lost in some forms of metastatic cancer, and is correlated with poor prognosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

DACH1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_080759.6

BS2

High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6 link	c.241_243dupGGC	p.Gly81dup	conservative_inframe_insertion	Exon 1 of 11	ENST00000613252.5	NP_542937.3	Q9UI36-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DACH1	ENST00000613252.5 link	c.241_243dupGGC	p.Gly81dup	conservative_inframe_insertion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1	Q9UI36-2
DACH1	ENST00000619232.2 link	c.241_243dupGGC	p.Gly81dup	conservative_inframe_insertion	Exon 1 of 12	5		ENSP00000482797.1	Q9UI36-1
DACH1	ENST00000706274.1 link	c.-219_-217dupGGC		upstream_gene_variant				ENSP00000516320.1	A0A994J7Q8

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

178

AN:

143512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000206

Gnomad ASJ

AF:

0.000295

Gnomad EAS

AF:

0.00254

Gnomad SAS

AF:

0.000662

Gnomad FIN

AF:

0.00338

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00167

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00174

AC:

1889

AN:

1085828

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

928

AN XY:

519204

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

19946

American (AMR)

AF:

0.00199

AC:

AN:

8034

Ashkenazi Jewish (ASJ)

AF:

0.000505

AC:

AN:

13856

East Asian (EAS)

AF:

0.00295

AC:

AN:

23766

South Asian (SAS)

AF:

0.000642

AC:

AN:

20258

European-Finnish (FIN)

AF:

0.00203

AC:

AN:

28630

Middle Eastern (MID)

AF:

0.00102

AC:

AN:

2954

European-Non Finnish (NFE)

AF:

0.00172

AC:

1588

AN:

925486

Other (OTH)

AF:

0.00205

AC:

AN:

42898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

167

250

334

417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00123

AC:

177

AN:

143602

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

69836

show subpopulations

African (AFR)

AF:

0.000512

AC:

AN:

39068

American (AMR)

AF:

0.000137

AC:

AN:

14566

Ashkenazi Jewish (ASJ)

AF:

0.000295

AC:

AN:

3388

East Asian (EAS)

AF:

0.00254

AC:

AN:

4718

South Asian (SAS)

AF:

0.000663

AC:

AN:

4528

European-Finnish (FIN)

AF:

0.00338

AC:

AN:

8882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00167

AC:

109

AN:

65330

Other (OTH)

AF:

0.00

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over